treatment for NOS+/+: am I doing too much or little?

I've suspected the NOS mutation long before my results revealed I am +/+ for it. So, for the last three weeks (I think) I've been taking various aminos to support the NOS pathway, despite it being a lower priority mutation according to Yasko. My reason for doing this is that I have so many toxins, and ammonia, in my system that I can't just let them sit there.

As with every other supplement bar d-ribose (which helps very slightly with energy - I'd say about 10% maximum) I'm only feeling worse, though; although this could be for any number of reasons, such as the CFS not responding, other supplements interacting with things, hypothyroidism, stress levels etc.

Anyway, I've based my NOS treatment on accounts I've read in this forum. My memory is sketchy, but suffice it to say I'm taking them all because of their relationship with one another; for example I'm taking supplement y because supplement x increases the need for it.

So, here's what I'm doing (note that I am taking the recommended amount given on the packet)
daily; either first thing in the morning, or between breakfast and lunch
l-citrulline
A-AKG
l-ornithine
l-lysine
BCAAs

Every 3 days I take 3 sprays of HHI Amino Assist, although this contains methionine, which I'm deficient in but I think supposed to be avoiding (forgtten why, silly me), in addition to tyrosine and tryptophan, which my UEE/UAA showed high excretions of (I am taking T4 and T3 thyroid medication, which does not appear to be getting absorbed, which may account for the high secretions of tyrosine. I was also trialing the SSRI sertraline at the time, which may account for the elevated tryptophan).

I am also taking l-glutamine because of leaky gut, despite the controversy. I'm not sure if that has any mitigating factors on the other aminos.

So, what does anyone think? Is this too much? Is it too soon to say? Would it be worth my while getting another UAA/UEE?

I can't comment on most of these supps. But if you can trace your 3 weeks of feeling worse to when you added things, and you're not feeling significantly better in any way, I'd either stop everything and let your system get rid of it, then add them back in one at a time, w/ enough time to see how you respond, minimum 3 days, probably. Or, alternatively, take things out one at a time, and see if something shifts.

You might need more B12 than the hydroxy is supplying. I know Yasko uses it, but I and others haven't benefited from it. Heartfixer references it at the following link. However his examples are about the relationship of COMT and VDRtaq in different combinations. You've not got the COMT, but this might suggest a switch to methyl from hydroxy B12. Just above this VDR reference, there is this:

If MTRR is (+/+) or (+/-), methyl-B12 formation will be compromised, homocysteine levels will be elevated, methylation in general will be compromised, and your physiology will be compromised.....

The VDR (Vitamin D Receptor) Fok defect affects blood sugar control and pancreatic function. It does not affect dopamine metabolism. Dr. Yasko recommends Vitamin K and generalized support of pancreatic function and sugar regulation (low carbohydrate diet, supplementation with chromium, etc.) when the VDR Fok abnormality is an issue.

Phosphatidylcholine, or as a less expensive alternative, Phosphatidylserine 100 mg daily, to stimulate the BHMT reaction....Phosphatidylserine can be used in combination with the methyl donor DMAE as Pedi-Activ, one daily.
2. TMG can be used to stimulate BHMT (but not in COMT (+/+) individuals, who will be sensitive to free methyl groups).

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When I uncovered my pyroluria I added the supps: P5P, minerals, and TMG. Five nights later I lay in bed and suddenly had a different feeling about life. That was the moment this methylation pathway research and treatment saga shifted from being an impossible burden I could barely manage, let alone make sense of, into an interesting challenge. A radical shift. this positivity has remained. I recently got it that the real shift was probably due to the TMG, the first thing I'd done to impact my methylation cycle.

Re your thyroid. You say you're not absorbing it. How do you know? Have you been tested for reverse T3 (rT3)? rT3 will indicate if you're not absorbing. I spent the first 5 years of my illness trying to get the right sort of thyroid. I went from synthroid to various combinations of Armour, T3, T4. The T3,4 were always time-released, the compounding chemist rather insisted on this. Eventually I discovered Dr. John Lowe, who spent 25 years looking at thyroid and FMS. I switched to T3 only, not time-release. I now take it in split doses through the day. Finally I'm getting the proper amount of thyroid. And since my methylation is improving, I've been able to lower it. OK, that's all I can do . cheers, ahmo

@ahmo
Thanks so much for your continued help . I'm going to bed now, so will get back to you properly tomorrow. I'll just say now, though, that I started the candida protocol (ACV, coconut oil, lemon juice, removing virtually all sugars from my ydiet) a month ago, as well as began using mag chloride oil, seriphos, and a few others. As I don't detoxify properly, I wonder if the candida protocol caused me to crash? If so, wouldn't that require more stuff for NOS?

Yes, this makes sense, you could be in a detox crash. Back to the detox strategies: full bath w. bicarb, footbaths w/ bicarb, clay, charcoal; coffee enemas. If you're constipated, even water enemas might help. Vit C can also go into footbaths, so you can take more than you'd be comfortable w/ orally.I see that coffee is on the high thiol list. I'm not sure what that means for you, whether it can be eliminated/balanced by the ammonia supps. I know when I retried a small dose of ALA recently, I really felt the sulfur. Maybe coffee is risky in any form, I don't know. Here's good coffee enema info. I hope I'm not repeating myself! http://www.mygutsy.com/the-ultimate-liver-detox-coffee-enemas/

Here's from heartfixer re NOS:

As the products of a compromised or genetically abnormal NOS system are the free radicals superoxide and peroxynitrite, aggressive antioxidant supplementation makes sense here (while a broad spectrum program of antioxidant supplementation is always wise, we specifically use Vitamin C to neutralize superoxide and 5-methyl folate to neutralize peroxynitrite).

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And here's Yasko, not much. I guess you attend to it as if it's CBS or SUOX.

The NOS (nitric oxide synthase) enzyme is located in the urea cycle, where it helps with ammonia detoxification. With NOS +/ +, there is reduced enzyme activity, producing an additive effect with CBS upregulations to result in the generation of higher levels of ammonia.
Some research in the medical literature suggests that omega 3 EFAs may limit NOS activity so I recommend using an EFA mixture with omega 3:6:9 only every other day, and alternating it with a different source of omega 3 fatty acids, such as DHA. These essential fatty acids optimize membrane fluidity, and by alternating them, you limit excess omega 3 which can interfere with the NOS enzyme. Since inefficient NOS activity can strain the urea cycle, leading to ele- vated ammonia levels, this method provides the fats you need without impacting NOS. Those without NOS mutations can consume omega 3’s daily. In addition, consuming a lower protein diet and Stress Foundation RNA (once or twice daily) also helps to support the urea cycle.

I suggest alternating the fatty acids the body needs, because in my clinical ex- perience I’ve noticed that with NOS + there is difficulty processing lipid donors. We all need certain lipids for a variety of bodily functions, so the key here is to use the donors mentioned below in moderation or as recommended in the supplement lists, not to eliminate them altogether.
Transdermal creams; Lipoceutical EDTA; Lipoceutical glutathione; High doses of EFA; CoQ10; ALA; Idebenone

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Re B vitamins, I think from another conversation, here's Freddd:

http://forums.phoenixrising.me/inde...-minus-100-pounds.25788/page-2#post-403Freddd: I am taking no extra B1, B2 or b3, just the amount in the low dose b-complex mentioned before; 10-20mg or so each per day in 2 doses. All three increased the amount of potassium and folate needed and reduced actually healing till at the end I couldn’t take enough of either and healing was going backwards. I am remaining quite stable now at about 1500mg of potassium and 4-6mg of Metafolin. I have thickening of my nails again at some point some months ago when I discontinued the extras, my actual cell formation increased. The requirements for 3000+mg of potassium and 20+mg of Metafolin came down in a few days after I discontinued the extra bs. ....I suggest that a low dose b-complex without folic acid and without CyCbl, E, C, A, D.........NatureMade B-complex with C, List # 1338. This has 15mg of thiamin,10.2mg of Riboflavin and 50mg of Niacin, 5mg b-6 and 10mg pantothenic acid.

When I uncovered my pyroluria I added the supps: P5P, minerals, and TMG. Five nights later I lay in bed and suddenly had a different feeling about life. That was the moment this methylation pathway research and treatment saga shifted from being an impossible burden I could barely manage, let alone make sense of, into an interesting challenge. A radical shift. this positivity has remained. I recently got it that the real shift was probably due to the TMG, the first thing I'd done to impact my methylation cycle.

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I'm taking P5P (107% RDA) because I don't get any in my diet, although Yasko says to limit all forms of b6 if you have NOS.

I tried TMG last year for about 3 months, before I started getting really sick. It made no difference, that I'm aware, but then again I wasn't as sick then as I am now. I've got DMG on order, though, as this is the one Yasko prefers. I wouldn't rule out trying TMG again, though.

Re your thyroid. You say you're not absorbing it. How do you know? Have you been tested for reverse T3 (rT3)? rT3 will indicate if you're not absorbing. I spent the first 5 years of my illness trying to get the right sort of thyroid. I went from synthroid to various combinations of Armour, T3, T4. The T3,4 were always time-released, the compounding chemist rather insisted on this. Eventually I discovered Dr. John Lowe, who spent 25 years looking at thyroid and FMS. I switched to T3 only, not time-release. I now take it in split doses through the day. Finally I'm getting the proper amount of thyroid. And since my methylation is improving, I've been able to lower it. OK, that's all I can do . cheers, ahmo

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My T4 and TSH levels have been dropping for over 2 years, despite me taking 100mcg T4 daily. This could also be due, though, to copper and iron anemia, as although I was taking iron (the bisglycinate form, which I didn't know until several months ago fed gut bugs) and copper with zinc, according to my UAA/UEE and UTM other issues seem to be preventing me from absorbing any of them.

In May last year, when my T4 dropped to 12 and my TSH was at 1, my GP finally agreed to put me on T3. I reduced my T4 to 50mcg and over a month worked up to 50mcg T3. Mt T4 and TSH are now 5 and 0.25, respectively; way below acceptable levels of normal. Obviously, the T3 will suppress the TSH anyway, and as I'm on even less T4 that will continue to be low. But my hypo symptoms are getting worse; I have constant patchy eyebrow loss, am mostly always cold, weight gain (although I am now intermittently losing weight for seemingly no reason; could be a water issue), my PCOS is worse, brain fog and fatigue worse... I tried T3 only for about a week, but saw no improvements. I think I'll try it again, as I may ahve a rT3 problem. I was tested for rT3, which apparently was normal, but I only spoke to my GP over the phone, and I've twice asked for print-outs but have never receieved them.

@ahmo How much vitamin c and 5-methylfolate? I take anywhere between 1000-5000% RDA vitamin c, and have been taking Solgar Metafolin (which is l-methylfolate, and approx 8000%RDA) for five days.

BH4 is also suggested, but I cannot get it shipped to where I live. The best I can do is royal jelly, and Yasko's A1298c+ Liver compound, which I have reservations (perhaps unfounded) about because it contains milk thistle and dandelion, which are sulforous. HHI also does a CBS/NOS compound which contains l-biopterin, but it's out of stock.

Another major concern, now, is about arginine. In a private conversation, @caledonia quoted heartfixer:

In a BH4 dependent reaction, Nitric Oxide Synthase (NOS) converts Arginine in to Nitric Oxide, the molecule that resists plaque formation, vasospasm, and abnormal clotting. If you can make and maintain Nitric Oxide then you will not develop cardiovascular disease. If you have cardiovascular disease and if we can successfully reboot your Nitric Oxide system, than we can stabilize your disease. Every maneuver in drug and non-drug cardiovascular medicine that improves patient symptomatic status and outcome works on this system. Every risk factor (or causative factor for cardiovascular disease) compromises Nitric Oxide generation or maintenance. NOS is also involved in ammonia detoxification, a job that distracts it from its Nitric Oxide generating duties and which uses up BH4. Without adequate levels of BH4 Nitric Oxide Synthase will not convert Arginine in to beneficial Nitric Oxide, but rather in to undesirable free radical species such as superoxide or peroxynitrite.

I think you are on the rite track for glutamine/glutamic acid supplementation but instead of taking them why don't you try AKG instead. AKG is alpha keto-glutarate, a glutamine molecule with the NH3 ammonia group taken out so in the body it works as an ammonia scavenger, combining with NH3 and then becoming glutamine. Your body shud prefer that.

...Btw is there a reason why your glutamine is high ? The GI tract gets first look at all the glutamine that enters the body and your GI tract itself needs alot of it. Most glutamine is absorbed by the gut b4 it even enters the blood stream so to have high circulating glutamine suggests that your intestinal permeability is very poor and it is letting alot of stuff thru directly into the blood w/o actually processing it. It's a vicious cycle from there. There liver gets over burdened and toxins in the blood accumulate in the CNS and brain.

Another thing I wud recommend is HMB (hydroxy methyl butyrate) along w AKG. It reduces muscle catabolism alot and that takes alot of stress off the liver while it is trying to sort things out w the gut.

Glutamine is a key step in healing from ME but if your ME is too far along it can be counterproductive. Alot of ME has to do with timing.

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Until today, I was taking glutamine for about three weeks, in desperate hope it would help my leaky gut, but I've only felt worse. I think my gut is just too leaky and it may have resulted in situation cited with the black emboldened text. I was hoping I could still continue with the A-AKG, but without adequate BH4 I'm concerned that I cannot.

I wonder if HMB would be an option for my over-stressed liver (but that's a different topic lol)?

on_noes, Vegas has some informative messages about the benefits of bifidobacteria with respect to reducing ammonia levels. Some of the information is in the thread about sulfites/sulfates, but there's another thread, too.

The first time I read through his messages I missed that he mentioned something about riboflavin (B2) deficiency being involved, too. What a coincidence.

@Violeta thanks for that Oh Lawdy...that's a huge thread, and skimming through it has raised more questions than answers (not blaming you personally, or anyone else for that matter). I now find myself in another quandary about the gut pathogens. I have systemic candida and perhaps h-pylori, in addition to a worm (probably a rope worm; it was listed as 'unidentified' on the stool test), the first of which I am trying to treat. But apparently gut pathogens help with NOS issues? Eeek! Hmmm...

I am lactose intolerant, so culturing anything isn't exactly an option. But I'll certainly look the bifido's. I was already taking some of them, rotating them daily, but over the last month I've significantly cut down because I was concerned they were exaccerbating my bloating, or at best not even being absorbed. I've certainly felt worse since cutting down on them, but then again I've made a lot of changes over the last month (which I know is unwise, but my desperation gets the better of me much of the time and I don't feel in control of it) I'll re-introduce them and see.

I am using Natren bifido factor, which is carried on garbanzo bean, and I stopped culturing it. I do find that bloating is worse, but from gardening I realize that when you compost soil you break it up and it takes up more space. You have to get the bacteria in there to start to ferment the stuff, it's not a pretty picture.

The thread is really long, I know how overwhelming that can be. It lead to something else, too, resistant starch. A lot of people are using potato starch from Bob's Red Mill, but I am going to use konjac, which is glucomannan. It supplies a good substrate for the growth of the good bacteria.

The good bacteria in the gut are what should take care of candida. I read about h pylori along the way, too, I'll see if I can find that. I think correctly the terrain of the gut will deal with parasites, too.

@Violeta thanks for your continued help. This is crazily confusing for me right now and, currently being in a state of very high anxiety, I see a long thread, get several posts into it, find information that contra-indicates my other health issues (if it doesn't contra-indicate hypothyroid and adrenals then it contraindicates hypoglycemia or PoTS or PCOS; if it doesn't contra-indicate NOS or CBS then it contraindicates MTRR or BHMT; etc) and I become too distressed to persvere reading. I appreciate that may sound silly and defeatist, but until someone has experienced extreme anxiety they may not ubnderstand how utterly debiltating it can be.

edit: as the Natren isn't readily available in the UK, I've looked into some other probiotics. One is Biocare L.acidophilus & B.bifidum, but it contains F.O.S, which I know nothing about. The text says

Fructooligosaccharides (F.O.S.) when ingested, provide a specific food source for the growth of friendly intestinal bacteria

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so it's looks to be a beneficial thing, but whether or not it would be beneficial for me I have no clue.

@Violeta thanks for your continued help. This is crazily confusing for me right now and, currently being in a state of very high anxiety, I see a long thread, get several posts into it, find information that contra-indicates my other health issues (if it doesn't contra-indicate hypothyroid and adrenals then it contraindicates hypoglycemia or PoTS or PCOS; if it doesn't contra-indicate NOS or CBS then it contraindicates MTRR or BHMT; etc) and I become too distressed to persvere reading. I appreciate that may sound silly and defeatist, but until someone has experienced extreme anxiety they may not ubnderstand how utterly debiltating it can be.

edit: as the Natren isn't readily available in the UK, I've looked into some other probiotics. One is Biocare L.acidophilus & B.bifidum, but it contains F.O.S, which I know nothing about. The text says

so it's looks to be a beneficial thing, but whether or not it would be beneficial for me I have no clue.

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Are you reading the B2 thread or the sulfite/sulfate thread? The B2 thread is the one that is so long (37 pages).

This is something from the sulfite/sulfate ammonia thread:

Consider trying Bifidobacterium strains, infantis and bifidum; these should be singularly cultured in milk for 24 hours. These will lower pH in the large intestine and dramatically reduce ammonia levels, inhibit the growth of pathogenic organisms, increase SCFA production, increase LAB numbers in the proximal bowel, inhibit/kill H. Pylori in the stomach.

Vegas, who recommends the bifidobacterium, says it's better to take plain bifido, no l acidophilus. But if that's all you can get, it's better than nothing. I'm not sure about FOS, at the very least I doubt if it's harmful.

I know what you mean about the anxiety and not being able to read long messages or threads.

I'm surprised no one mentioned B3, as Ben Lynch says that calms one down when they've overdone folate and B12.

Are you reading the B2 thread or the sulfite/sulfate thread? The B2 thread is the one that is so long (37 pages).

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The sulfate/sulfite one. I generally find anything beyond 1 page, and with long, detailed content, overwhelms me. Prior to getting sick and super anxious I used to be the exact opposite with, and would gravitate towards fine details and complex texts. I used to love medical texts and sciencey stuff, spending many happy hours engrossed in 10+page threads about a complex topic... and then boom: 180% change. Something definitely happened to my neurotransmitters (gonna blame the MAO SNP). But I digress, hah

Consider trying Bifidobacterium strains, infantis and bifidum; these should be singularly cultured in milk for 24 hours. These will lower pH in the large intestine and dramatically reduce ammonia levels, inhibit the growth of pathogenic organisms, increase SCFA production, increase LAB numbers in the proximal bowel, inhibit/kill H. Pylori in the stomach.

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Vegas, who recommends the bifidobacterium, says it's better to take plain bifido, no l acidophilus. But if that's all you can get, it's better than nothing. I'm not sure about FOS, at the very least I doubt if it's harmful.

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I'll definitely try those out. If I can find dairy free versions, that is.

I'm surprised no one mentioned B3, as Ben Lynch says that calms one down when they've overdone folate and B12.

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I've read that, too, but I'm confused which form. Niacin? Niacinamide? Nicotinamide? NAD? NADH?
I've been taking 5mg NADH per day every other day for 3 months, and more on the days when I take HHI A1298c+ LiverSupport, but it hasn't stopped me deteriorating.

Which form? I have the pantothenic acid form in capsules, and it's in the Jarrow liquid freebase carnitine (although I'm going to trial stop it because I've read elsewhere here it can interfere with the thyroid, amongst other things...but that belongs in a different post which I'm going to make later).

I bought milk thistle, then learned it was sulfurous, so it's another of the unused supps in my cupboard.

NCM of GAPS, counsels against using FOS, a prebiotic, which feeds both good and bad bacteria. That's why I decided against Ben Lynch's probiotic supp.

I'm using generally 1 tsp, 5 gm, ascorbic acid in my footbaths. When shifting methylfolate or detoxxing, this can go up to 1-2 Tbs.

Mfolate: I was very concerned re increasing doses, and looked for hours on threads to understand how much I should be aiming for, and how to get there. Since getting a response from Fredd re rate of increasing dosage, I've been steadily moving up by 100-200mcg every day or 2. I'm currently at about 8.5 mg, including the 400 I get in the Swanson's B complex linked below. I had some 800mcg Solgar metafolin, which I cut into 4, giving me 200mcg doses. I also have some .5 mg (500mcg) caps, so I first add 200 mcg, then, if that's ok, in the early days, I'd add another 200, or now I might go further, up to the 500mcg., which is an increase of 300mcg. About 3 times I've gotten a reaction: verging on anxiety, needing K+, uncomfortable feeling. I considered taking B3 to calm it down. But instead, after taking the K+ and Mg I needed, I stuck a B12 under my tongue and went back to sleep. This has worked brilliantly for me. I'm currently at 9mg MB12, 7.5 AdB12. Freddd suggests these should be generally similar doses, and that typically, no more than 10mg AdB12 is necessary.

I use glutamine. I put it in footbaths. But I'm now also adding it to the clear water enema following on from my coffee enemas. I agree w/ those who question Yasko's understanding that it becomes glutamate. That's not my experience.

Are you eating fermented foods? Your MAO++ suggests that's not a good idea. Forgive me if we've already had a histamine conversation....

I'd been using high dose Bs for many years. CFS expert Dr. Jacob Teitelbaum recommends 500mg B1 for anxiety. Also large B3 doses. Following Freddd's comments re lowering B's for decreasing potassium needs, I anxiously (!) reduced mine. No increase in anything negative. But with the significant decrease in sulfur from the B's, I eliminated a glitch in my shoulder, similar to the same response in the opposite shoulder when I eliminated sulfur from my diet. I now use very low dose B complex.

I am taking no extra B1, B2 or b3, just the amount in the low dose b-complex mentioned before; 10-20mg or so each per day in 2 doses. All three increased the amount of potassium and folate needed and reduced actually healing till at the end I couldn’t take enough of either and healing was going backwards. I am remaining quite stable now at about 1500mg of potassium and 4-6mg of Metafolin. I have thickening of my nails again at some point some months ago when I discontinued the extras, my actual cell formation increased. The requirements for 3000+mg of potassium and 20+mg of Metafolin came down in a few days after I discontinued the extra bs. ....I suggest that a low dose b-complex without folic acid and without CyCbl, E, C, A, D.........NatureMade B-complex with C, List # 1338. This has 15mg of thiamin,10.2mg of Riboflavin and 50mg of Niacin, 5mg b-6 and 10mg pantothenic acid.

The sulfate/sulfite one. I generally find anything beyond 1 page, and with long, detailed content, overwhelms me. Prior to getting sick and super anxious I used to be the exact opposite with, and would gravitate towards fine details and complex texts. I used to love medical texts and sciencey stuff, spending many happy hours engrossed in 10+page threads about a complex topic... and then boom: 180% change. Something definitely happened to my neurotransmitters (gonna blame the MAO SNP). But I digress, hah

I'll definitely try those out. If I can find dairy free versions, that is.

I've read that, too, but I'm confused which form. Niacin? Niacinamide? Nicotinamide? NAD? NADH?
I've been taking 5mg NADH per day every other day for 3 months, and more on the days when I take HHI A1298c+ LiverSupport, but it hasn't stopped me deteriorating.

How does B3 help with NOS, though?

Which form? I have the pantothenic acid form in capsules, and it's in the Jarrow liquid freebase carnitine (although I'm going to trial stop it because I've read elsewhere here it can interfere with the thyroid, amongst other things...but that belongs in a different post which I'm going to make later).

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I don't know where the idea that carnitine interferes with thyroid, but it helps get nutrients into the cell where they are needed, it only gave me more energy. You just have to make sure you are ingesting enough carbs when you take it.

I mentioned the B3 because of some of your other symptoms. Did you know that B3 is good for loss of appetite?

Sometimes you have to go by symptoms and not by genetic testing, as symptoms might be revealing something else going on. Symptoms can be good clues.

I am using Natren bifido factor, which is carried on garbanzo bean, and I stopped culturing it. I do find that bloating is worse, but from gardening I realize that when you compost soil you break it up and it takes up more space. You have to get the bacteria in there to start to ferment the stuff, it's not a pretty picture.

The thread is really long, I know how overwhelming that can be. It lead to something else, too, resistant starch. A lot of people are using potato starch from Bob's Red Mill, but I am going to use konjac, which is glucomannan. It supplies a good substrate for the growth of the good bacteria.

The good bacteria in the gut are what should take care of candida. I read about h pylori along the way, too, I'll see if I can find that. I think correctly the terrain of the gut will deal with parasites, too.

No, I gave up on resistant starch. I just take Garden of Life probiotic and am happy that that no longer bothers me. How have you been doing and have you tried anything new? I really should try taking the konjac, I hate letting it go to waste.